Rethinking clinical trials of transcranial direct current stimulation: Participant and assessor blinding is inadequate at intensities of 2mA

Copyright @ 2012 The Authors. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and 85 reproduction in any medium, provided the original author and source are credited. The article was made available through the Brunel University Open Access Publishing Fund.Background: Many double-blind clinical trials of transcranial direct current stimulation (tDCS) use stimulus intensities of 2 mA despite the fact that blinding has not been formally validated under these conditions. The aim of this study was to test the assumption that sham 2 mA tDCS achieves effective blinding. Methods: A randomised double blind crossover trial. 100 tDCS-naïve healthy volunteers were incorrectly advised that they there were taking part in a trial of tDCS on word memory. Participants attended for two separate sessions. In each session, they completed a word memory task, then received active or sham tDCS (order randomised) at 2 mA stimulation intensity for 20 minutes and then repeated the word memory task. They then judged whether they believed they had received active stimulation and rated their confidence in that judgement. The blinded assessor noted when red marks were observed at the electrode sites post-stimulation. Results: tDCS at 2 mA was not effectively blinded. That is, participants correctly judged the stimulation condition greater than would be expected to by chance at both the first session (kappa level of agreement (κ) 0.28, 95% confidence interval (CI) 0.09 to 0.47 p = 0.005) and the second session (κ = 0.77, 95%CI 0.64 to 0.90), p = <0.001) indicating inadequate participant blinding. Redness at the reference electrode site was noticeable following active stimulation more than sham stimulation (session one, κ = 0.512, 95%CI 0.363 to 0.66, p<0.001; session two, κ = 0.677, 95%CI 0.534 to 0.82) indicating inadequate assessor blinding. Conclusions: Our results suggest that blinding in studies using tDCS at intensities of 2 mA is inadequate. Positive results from such studies should be interpreted with caution.GLM is supported by the National Health & Medical Research Council of Australia ID 571090

Influence of a walking aid on temporal and spatial parameters of gait in healthy adults

This is the post-print version of the final paper published in PM&R. The published article is available from the link below. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. Copyright @ 2014 Elsevier B.V.Objective - To determine the effect of using a walking aid on temporal and spatial parameters of gait when used for balance versus support on the dominant and nondominant hand side. Design - Repeated measures observational study design. Setting - University gymnasium. Participants - Twenty-seven healthy male and female adults of mean ± standard deviation age 44.74 ± 10.00 years. Methods - Five walking conditions (C) were completed by all participants on the GAITRite pressure mat. Normal walking (C1), walking with a cane in the dominant hand (C2) and nondominant hand (C3) as if using for balance, walking with a cane in the dominant hand (C4) and nondominant hand (C5) while allowing approximately 10% of the body weight through the cane. Main Outcome Measurements - Temporal measurements (swing time, stance time, single limb support time, double limb support time) as percentage of a gait cycle and the base of support for the left and the right foot for all 5 walking conditions. Results - A significant difference (P < .001) was observed between C1, C2, and C3 in percentage swing time and percentage stance time of the ipsilateral side, and in percentage single limb support time of the contralateral side. The double limb support time was significantly different (P ≤ .04) for both ipsilateral and contralateral sides. Comparisons among C1, C4, and C5 demonstrated significance (P < .001) for all variables. Post hoc analysis showed significance between C1 and C4, and C1 and C5 for all variables except percentage stance time of the ipsilateral side and percentage single limb support of the contralateral side. Conclusions - In healthy adults, use of a cane for balance modifies swing and stance parameters of the ipsilateral side and does not affect the base of support formed by the feet. When used for support, the cane alters the swing and stance parameters, and also the base of support formed by the feet

Transcranial direct current stimulation of the motor cortex in the treatment of chronic non-specific low back pain. A randomised, double-blind exploratory study

This exploratory study aimed to test the proof of principle that active anodal transcranial direct current stimulation (tDCS) applied to the motor cortex reduces pain significantly more than sham stimulation in a group of participants with chronic non-specific low back pain

Re-evaluating the measurement and influence of conscious movement processing on gait performance in older adults: development of the Gait-Specific Attentional Profile

Background. Recent decades have seen increased interest in how anxiety–and associated changes in conscious movement processing (CMP)–can influence the control of balance and gait, particularly in older adults. However, the most prevalent scale used to measure CMP during gait (the Movement-Specific Reinvestment Scale (MSRS)) is generic (i.e., non-gait specific) and potentially lacks sensitivity in this context. Methods. In a preliminary study, we first sought to evaluate if MSRS scores associated with the number of CMP-related thoughts self-reported by older adults while walking. The next aim was to develop and validate a new questionnaire (the Gait-Specific Attentional Profile, G-SAP) capable of measuring gait-specific CMP, in addition to other attentional processes purported to influence gait. This scale was validated using responses from 117 (exploratory) and 107 (confirmatory factor analysis) older adults, resulting in an 11-item scale with four sub-scales: CMP, anxiety, fall-related ruminations, and processing inefficiencies. Finally, in a separate cohort of 53 older adults, we evaluated associations between scores from both the GSAP CMP subscale and the MSRS, and gait outcomes measured using a GAITRite walkway in addition to participants’ fall-history. Results. MSRS scores were not associated with self-reported thoughts categorised as representing CMP. In regression analyses that controlled for functional balance, unlike the MSRS, the G-SAP subscale of CMP significantly predicted several gait characteristics including velocity (p=.033), step length (p=.032), and double-limb support (p=.015). Significance. The G-SAP provides gait-specific measures of four psychological factors implicated in mediating the control of balance and gait. In particular, unlike the MSRS, the G-SAP subscale of CMP appears sensitive to relevant attentional processes known to influence gait performance. We suggest that the G-SAP offers an opportunity for the research community to further develop understanding of psychological factors impacting gait performance across a range of applied clinical contexts

Transcranial direct current stimulation of the motor cortex in the treatment of chronic nonspecific low back pain: A randomized, double-blind exploratory study

Objectives: To test the proof of principle that active anodal transcranial direct current stimulation (tDCS) applied to the motor cortex reduces pain significantly more than sham stimulation in a group of participants with chronic nonspecific low back pain. Methods: The study utilized a within-participants sham-controlled, interrupted time series design. A sample of 8 participants was recruited. After 3 days of baseline measures, patients entered a 15-day experimental period (Mondays to Fridays) for 3 consecutive weeks. During this period each patient received sham stimulation daily until a randomly allocated day when active stimulation was commenced. Active stimulation was then given daily for the remaining days of the experimental period. Both the participants and the assessors were blinded. The primary outcomes were average pain intensity and unpleasantness in the last 24 hours measured using a visual analogue scale. Secondary outcomes included self-reported disability, depression and anxiety, a battery of cognitive tests to monitor for unwanted effects of stimulation, and patients\u27 perceptions of whether they had received active or sham stimulation. Data were analyzed using generalized estimating equations. Results: No significant effect was seen in the primary outcomes between active and sham stimulation (average pain intensity P=0.821, unpleasantness P=0.937) or across any other clinical variables. There was evidence that patients may have been able to distinguish between the active and sham conditions (P=0.035). Discussion: These results do not provide evidence that tDCS is effective in the treatment of chronic back pain. The use of a small convenience sample limits the generalizability of these findings and precludes definitive conclusions on the efficacy of tDCS in chronic nonspecific low back pain

Assessors judgements of skin redness at the electrode site, for each stimulation condition.

<p>Assessors judgements of skin redness at the electrode site, for each stimulation condition.</p

A roadmap to generate renewable protein binders to the human proteome

Despite the wealth of commercially available antibodies to human proteins, research is often hindered by their inconsistent validation, their poor performance and the inadequate coverage of the proteome. These issues could be addressed by systematic, genome-wide efforts to generate and validate renewable protein binders. We report a multicenter study to assess the potential of hybridoma and phage-display technologies in a coordinated large-scale antibody generation and validation effort. We produced over 1,000 antibodies targeting 20 SH2 domain proteins and evaluated them for potency and specificity by enzyme-linked immunosorbent assay (ELISA), protein microarray and surface plasmon resonance (SPR). We also tested selected antibodies in immunoprecipitation, immunoblotting and immunofluorescence assays. Our results show that high-affinity, high-specificity renewable antibodies generated by different technologies can be produced quickly and efficiently. We believe that this work serves as a foundation and template for future larger-scale studies to create renewable protein binders